Doxycycline versus azithromycin for the treatment of anorectal Chlamydia trachomatis infection in women concurrent with vaginal infection (CHLAZIDOXY study): a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection. METHODS: We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464. FINDINGS: Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21-0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group. INTERPRETATION: The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Multicentric evaluation of BioFire FilmArray Pneumonia Panel for rapid bacteriological documentation of pneumonia.

OBJECTIVES: To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. METHODS: This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. RESULTS: A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%-96.5%) and 96.0% (95% CI 95.5%-96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log10 in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥106 DNA copies/mL grew significantly in culture. CONCLUSIONS: FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia.

Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia.

BACKGROUND: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). METHODS: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. RESULTS: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care. CONCLUSIONS: Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia.

Epidemiology and Appropriateness of Antibiotic Prescribing in Severe Pneumonia After Lung Resection.

BACKGROUND: Postoperative pneumonia (POP) is a severe complication of major lung resection. The objective of this study was to describe the current epidemiology and appropriateness of antibiotic prescriptions in severe POP, 4 years after implementation of an antimicrobial stewardship program that was based on weekly multidisciplinary review of all antibiotic therapies. METHODS: This study was a retrospective analysis of a prospectively collected database. It included all cases of severe POP occurring within 30 days after major lung resection of in a 1,500-bed hospital between 2013 and 2015. Criteria for severe POP were acute respiratory failure, severe sepsis, or a rapidly extensive pulmonary infiltrate. The study collected data on incidence, clinical outcomes, and microbiological analyses. Appropriateness of antibiotic prescribing was assessed by quality indicators previously validated in the literature. RESULTS: Over the study period, 1,555 patients underwent major lung surgery. Severe POP occurred in 91 patients (5.8%; confidence interval, 4.7%; 7.0%), with a mortality rate of 9.0% (8 of 91; confidence interval, 3.0%; 14.6%). In POP with positive microbiological results, the proportion of gram-negative bacteria other than Haemophilus was 76% (50 of 66 cases). All patients (91 of 91) had respiratory samples taken within 24 hours after the start of antibiotics; empiric therapy was concordant with the guideline in 80% (69 of 86), and it was switched to pathogen-directed therapy in 74% (46 of 62). In 71 of 91 patients (78%), the antibiotic duration was up to 7 days. CONCLUSIONS: This study reported a high proportion of gram-negative bacteria in severe POP. Four years after implementation of the program, quality indicators of antibiotic prescribing were all >70%. The rate of de-escalation to pathogen-directed therapy could be improved, however.

Impact of Sequential Culture Results on Diagnosis and De-Escalation of the Antibiotic Regimen in Joint and Bone Infections.

BACKGROUND: According to existing guidelines, orthopedic specimens collected in joint and bone infections (JBI) in our institution are cultured on several media sets and incubated for two, seven, and 14 days. The optimal timing for de-escalation of the first-line antibiotic combination according to the culture results needs to be defined. METHODS: Single-center, retrospective analysis of all adult patients with a first documented episode of JBI between May 2012 and April 2013. RESULTS: Ninety patients were included, 51 males (57%), median age 58 y (range 18-87 y), with prosthesis infection in 62 cases (69%). Rapidly growing pathogens (Staphylococcus aureus [n = 36] and Enterobacteriaceae [n = 12]) usually were diagnosed within two days, whereas coagulase-negative staphylococci (n = 25) and Propionibacterium acnes (n = 13) generally were identified after seven days (p < 10-5). Positive culture results at day 2 fit with definitive microbiological diagnosis in 95% of cases, and prolonged incubation led to the identification of additional micro-organisms in only four of 76 patients (5%) with day-2-positive cultures. Conversely, for those with negative two-day culture (n = 14), the seven-day culture allowed identification of less virulent pathogens in eight cases (57%). CONCLUSIONS: Our results suggest that, in JBI, de-escalation of the empirical antibiotic regimen can be based on micro-organisms identified on the two-day culture set. The impact of such a strategy on clinical outcomes, antibiotic consumption, and costs needs to be assessed in larger studies.

The value of molecular techniques to diagnose Ureaplasma urealyticum and Nocardia farcinica pleuropneumonia in a patient with diffuse large B-cell lymphoma.

An unusual case of pleural empyema related to Nocardia farcinica and Ureaplasma urealyticum, occurring after autologous haematopoietic stem cell transplantation in a 30-year-old patient with lymphoma, is reported. This case illustrates the role of repeated and comprehensive microbiological investigations and the contribution of molecular techniques in reaching the aetiological diagnosis.

Characterization of Streptococcus pyogenes isolates responsible for adult meningitis in France from 2003 to 2013.

Sixty-three cases of Streptococcus pyogenes meningitis in adults were studied. Three predominant emm types were associated with meningitis: emm1 (44%), emm3 (11%), and emm6 (11%). Streptococcal toxic shock syndrome and mortality rates were 40% and 38%, respectively.

High Frequency of Polymicrobial Infections After Surgical Resection of Malignant Bone and Soft Tissue Tumors: A Retrospective Cohort Study.

INTRODUCTION: Surgical resection of a malignant bone tumor (BT) or soft tissue tumor (STT), with or without prosthetic replacement, carries a high risk of developing postoperative infections. There is limited knowledge on the bacteriological spectrum of these postsurgical infections that necessitate empirical antibiotic therapy. The aim of this study was to analyze the incidence and microbiological features of site infections following BT or STT resection. METHODS: In this retrospective mono-center study, we analyzed the surgical and bacteriological data of all consecutive patients who developed an infection after surgical resection of a BT or STT between January 2010 and April 2014. RESULTS: Seventy-two consecutive patients who developed an infection on the site of surgical treatment for a BT (n = 42) or SST (n = 30) were included. Polymicrobism was frequently observed, more often associated with STTs (93%) than BTs (71%; P = 0.03). Gram-negative bacteria were more frequently isolated in STTs (55%) than in BTs (26%; P = 0.01) and non-prosthesis-associated infections (54%) than prosthesis-associated infections (29%; P = 0.04), whereas staphylococci were more frequently found in BTs (76%) than in STTs (52%; P = 0.03). Overall, we found gram negatives in 82% of early acute infections, 11% of chronic infections and 7% of late acute infections (P < 0.01). CONCLUSION: Postoperative infections in patients after surgical resection of BTs or STTs were often polymicrobial, especially following STTs. Causative bacteria were often gram negatives in STTs and non-prosthesis-associated infections, whereas staphylococci were predominant in BTs. Based on these findings, we recommend antibiotic coverage of both gram-positive and -negative bacteria with a combination of broad-spectrum antibiotics in STTs and antistaphylococcal antibiotics as first-line therapy in infections following BT surgery.

Adult invasive and noninvasive infections due to Streptococcus dysgalactiae subsp. equisimilis in France from 2006 to 2010.

We characterized 182 Streptococcus dysgalactiae subsp. equisimilis isolates and analyzed the epidemiological data on the corresponding infections. stG6, stG485, and stG6792 were the 3 most prevalent invasive emm types among the 27 different emm types recovered. High rates of antimicrobial resistance were observed for macrolides (26.4%) and tetracycline (34.6%).

Bacteremia caused by an undescribed species of Janibacter.

A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides.

Clonal spread of emm type 28 isolates of Streptococcus pyogenes that are multiresistant to antibiotics.

Fifty-three pharyngitis-related and invasive isolates of Streptococcus pyogenes that are resistant to bacitracin were collected. They were also resistant to streptomycin, kanamycin, macrolides, lincosamides, and streptogramin B. These multiresistant isolates were of emm type 28 and clonally related as shown by pulsed-field gel electrophoresis.

Epidemiological markers of group A streptococcal infections in France.

BACKGROUND & OBJECTIVES: A limited number of biotypes, T-types, and emm-types have been found to be associated with invasive isolates of group A streptococci, confirming the involvement of the M protein in virulence and its importance as an epidemiological marker. In this study, the epidemiological markers in the clinical isolates of group A streptococci were compared in invasive and non invasive isolates. METHODS: From 1998 to 2001, 141 invasive and 353 non invasive isolates in France were studied and their biotype, T-type, and emm-type were determined. RESULTS: The invasive isolates were mostly obtained from blood whereas the non invasive isolates were isolated from throat. Most of the isolates were of biotype 1. The invasive isolates were mostly of the T-type 1 associated with emm-type 1. The T-type 4 associated with emm-type 4 and the T-type 28 associated with emm-type 28 were also frequent. Invasive isolates responsible for puerperal sepsis and non invasive isolates were mostly of the T-type 28 associated with emm-type 28. INTERPRETATION & CONCLUSION: This study confirms the high prevalence of isolates of biotype 1, T-type 1, and emm-type 1 among invasive isolates of group A streptococci. The emm-type 28 associated with T-type 28 was frequently observed in non-invasive isolates. A prospective study is being conducted to update the prevalence of the different emm-types in France, which will be of importance for the development of future vaccines.

Isolation of sulfate-reducing bacteria from human thoracoabdominal pus.

To evaluate the prevalence of sulfate-reducing bacteria in septic processes, we searched for these bacteria by culture in 100 consecutive abdominal and pleural pus specimens. Twelve isolates were obtained from abdominal samples and were identified by a multiplex PCR as Desulfovibrio piger (formerly Desulfomonas pigra) (seven strains), Desulfovibrio fairfieldensis (four strains), and Desulfovibrio desulfuricans (one strain).

Bacteremia caused by Acinetobacter ursingii.

Acinetobacter ursingii has not been reported in infectious processes apart from its recent description as a new species. A bacteremia caused by A. ursingii in a patient with a pulmonary adenocarcinoma confirms that this microorganism is an opportunistic human pathogen. The isolate was susceptible to imipenem, aminoglycosides, rifampin, and fluoroquinolones.

Reclassification of the only species of the genus Desulfomonas, Desulfomonas pigra, as Desulfovibrio piger comb. nov.

The growth characteristics, DNA G+C content and sequences of 16S rDNA and the transcribed 16S-23S rDNA internal spacer were determined for Desulfomonas pigra ATCC 29098T, Desulfovibrio desulfuricans subsp. desulfuricans strains Essex 6T (= ATCC 29577T) and MB (= ATCC 27774) and 'Desulfovibrio fairfieldensis' ATCC 700045. Despite phenotypic differences (shape and motility) between Desulfomonas pigra and Desulfovibrio strains, the molecular analysis suggests that Desulfomonas pigra should be reclassified within the genus Desulfovibrio. Thus, the reclassification is proposed of Desulfomonas pigra, the type and only species of the genus, as Desulfovibrio piger comb. nov., which implies the emendation of the description of the genus Desulfovibrio.

Sulfate-reducing bacteria in human feces and their association with inflammatory bowel diseases.

We have searched for sulfate-reducing bacteria in the feces of 41 healthy individuals and 110 patients from a Hepato-Gastro-Enterology Unit using a specific liquid medium (Test-kit Labège, Compagnie Française de Géothermie, Orléans, France). The 110 patients were separated in 22 patients presenting with inflammatory bowel diseases and 88 patients hospitalized for other lower (n=30) or upper (n=58) digestive tract diseases. Sulfate-reducing bacteria were isolated from 10 healthy individuals (24%), 15 patients presenting with inflammatory bowel diseases (68%), and 33 patients with other symptoms (37%). A multiplex PCR was devised for the identification of Desulfovibrio piger (formerly Desulfomonas pigra), Desulfovibrio fairfieldensis and Desulfovibrio desulfuricans, and applied to the above isolates. The strains of sulfate-reducing bacteria consisted of D. piger (39 isolates), D. fairfieldensis (19 isolates) and D. desulfuricans (one isolate). The prevalence of D. piger was significantly higher in inflammatory bowel disease patients (55%) as compared to healthy individuals (12%) or patients with other symptoms (25%) (P<0.05).